DNA vaccine therapy for Alzheimer's disease: present status and future direction

Alzheimer's disease is the most common cause of dementia characterized by progressive neurodegeneration. Based on the amyloid cascade hypothesis, a vaccine therapy for Alzheimer's disease (AD) was developed as a curative treatment. In 1999, the amyloid beta (Abeta) reduction in AD model transgenic mice with active vaccination with Abeta peptide was first reported. Although the clinical trials of active vaccination for AD patients were halted due to the development of meningoencephalitis in some patients, from the analysis of the clinical and pathological findings of treated patients, the vaccine therapy is thought to be effective. Based on such information, the vaccines for clinical application of human AD have been improved to control excessive immune reaction. Recently, we have developed non-viral DNA vaccines and obtained substantial Abeta reduction in transgenic mice without side effects. DNA vaccines have many advantages over conventional active or passive immunization. In this article, we review conventional vaccine therapies and further explain our non-viral DNA vaccine therapy. Finally, we show some data regarding the mechanisms of Abeta reduction after administration of DNA vaccines. DNA vaccination may open up new avenues of vaccine therapy for AD.